Effect of modified formula Compound Biejia Ruangan Pills on hepatic fibrosis in rats induced by CCl4 and its mechanism / 中草药

ABSTRACT

Objective: To explore the possible effects and mechanism of modified Compound Biejia Ruangan Pills (MF-CBRP) on liver fibrosis induced by CCl4 in rats. Methods: SD rats were randomly divided into control group, model group, positive control (colchicine, 0.1 mg/kg) group, CBRP group (0.594 7 g/kg), MF-CBRP high-and low-dose (1.061 0 and 0.530 5 g/kg) groups. The rat model with liver fibrosis was established by sc injection CCl4 solution (dissolved in soybean oil), twice a week for six weeks except control group. The rats in the treatment groups were administered six weeks after the model establishment. At the end of the administration, the contents of serum biochemical, hydroxyproline (Hyp), lipid peroxidation, fibrosis factor, platelet-derived factor-α (PDGF-α), and connective tissue growth factor (CTGF) were measured and the pathological changes of liver tissue were examined by HE and Masson. The level of α-SMA and the expression of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by immunohistochemistry and RT-PCR. Results: The results showed that MF-CBRP improved the liver function significantly through reducing the level of ALT, AST, T-Bil, ALP, Hyp, HA, LN, PC-III, IV-C, and MDA (P < 0.05, 0.01), and increasing the content of S/L, TP, ALB, SOD, and GSH (P < 0.05, 0.01). MF-CBRP also reduced the expression of PDGF-α, CTGF, α-SMA, MMP-2, and TIMP-1 mRNA (P < 0.01) and improved the pathological changes of liver histopathology. Compared with CBRP, MF-CBRP anti-hepatic fibrosis effect was slightly weakened. Conclusion: The results suggested that MF-CBRP may against hepatic fibrosis by reducing oxidative stress, inhibiting collagen fibrillation, reversing hepatic stellate cell activation, and inhibiting the expression of hepatic growth factor. However its anti-fibrosis activity and mechanism was weaker than the original CBRP in a certain extent.